The overall goal of this proposal is to investigate the molecular and cellular biology of brain tumors and to link and integrate these efforts with clinical studies that are designed to optimize diagnosis, prognosis and treatment in infants, children, and adults with these neoplasms. The individual research proposals involve extensive collaboration and interaction among all of the principal investigators. Studies on DNA repair (Friedberg), molecular genetics (Bowcock/Nisen), proliferation (White), and the folate receptor (Kamen) in brain tumors utilize similar and complementary experimental modalities. A common centralized brain tumor registry, specimen bank and data base core will enable each of the investigators to compare and contrast their observations on the same set of specimens. All brain tumor specimens (pediatric and adult) from the University of Texas Southwestern Medical Center clinical facilities are funneled through Neuropathology (Drs. White and Burns), which will assure appropriate acquisition and standardized evaluation and processing of all necessary samples. Crucial to this proposal is the existence of a large clinical component that will provide a vast amount of patient-derived tumor samples for study, and the ability to optimize existing forms of therapy and allow for rapid application of basic science discoveries to preclinical and clinical trials. The establishment of a Brain Tumor Research Center will facilitate further development of additional research capabilities for basic, applied and clinical research, and specialized clinical training in the care of these patients at the University of Texas Southwestern Medical Center.